scholarly journals Evaluation and Immunolocalization of BMP4 and FGF8 in Odontogenic Cyst and Tumors

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Neeti Swarup ◽  
Meghanand T. Nayak ◽  
Zoya Chowdhary ◽  
Monica Mehendiratta ◽  
Shikha Khatana ◽  
...  
Keyword(s):  
Growth Factors ◽  
Tooth Development ◽  
Research Work ◽  
Odontogenic Cyst ◽  
Odontogenic Cysts ◽  
Fibroblast Growth Factor 8 ◽  
Nuclear Expression ◽  
Morphogenetic Protein ◽  
Ameloblastic Fibroma ◽  
Tooth Germs

Growth factors like bone morphogenetic protein 4 (BMP4) and fibroblast growth factor 8 (FGF8) play a major role in organogenesis and specifically in odontogenesis. They are also believed to have a role in oncogenesis. Thus, any discrepancies in their standard behavior and activity would lead to serious abnormalities including odontogenic cyst and tumors. The present research work investigated the expression of BMP4 and FGF8 in odontogenic tumors (OT) and cyst as well as developing tooth germs to elucidate their roles. Dental organs of various odontogenic stages and 30 OTs including solid multicystic ameloblastomas (SMA, 10 cases), ameloblastic fibroma (AF, 10 cases), odontogenic myxoma (OM, 10 cases), and odontogenic cysts: odontogenic keratocyst (OKC, 10 cases) were evaluated in both epithelial and mesenchymal components for the expression of BMP4 and FGF8 using immunohistochemistry. The epithelial nuclear expression of BMP4 was highest in OKC (9 cases) while FGF8 was highest in SMA (10 cases). The mesenchymal nuclear expression of both BMP4 (8 cases) (p=0.001) and FGF8 (9 cases) (p=0.045) were significantly high in OMs among all OTs. Both growth factors were actively expressed in different stages of tooth development. The expression of BMP4 and FGF8 corelates well with the proliferative component of the pathologies, indicating a possible role in the pathogenesis and progression.

scholarly journals Anti–USAG-1 therapy for tooth regeneration through enhanced BMP signaling

2021 ◽  
Vol 7 (7) ◽  
pp. eabf1798
Author(s):  
A. Murashima-Suginami ◽  
H. Kiso ◽  
Y. Tokita ◽  
E. Mihara ◽  
Y. Nambu ◽  
...  
Keyword(s):  
Tooth Development ◽  
Bmp Signaling ◽  
Tooth Agenesis ◽  
Tooth Regeneration ◽  
Missing Teeth ◽  
Morphogenetic Protein ◽  
Genetic Abnormalities ◽  
Direct Binding ◽  
Tooth Germs ◽  
Lipoprotein Receptor Related Protein

Uterine sensitization–associated gene-1 (USAG-1) deficiency leads to enhanced bone morphogenetic protein (BMP) signaling, leading to supernumerary teeth formation. Furthermore, antibodies interfering with binding of USAG-1 to BMP, but not lipoprotein receptor–related protein 5/6 (LRP5/6), accelerate tooth development. Since USAG-1 inhibits Wnt and BMP signals, the essential factors for tooth development, via direct binding to BMP and Wnt coreceptor LRP5/6, we hypothesized that USAG-1 plays key regulatory roles in suppressing tooth development. However, the involvement of USAG-1 in various types of congenital tooth agenesis remains unknown. Here, we show that blocking USAG-1 function through USAG-1 knockout or anti–USAG-1 antibody administration relieves congenital tooth agenesis caused by various genetic abnormalities in mice. Our results demonstrate that USAG-1 controls the number of teeth by inhibiting development of potential tooth germs in wild-type or mutant mice missing teeth. Anti–USAG-1 antibody administration is, therefore, a promising approach for tooth regeneration therapy.

Bone Morphogenetic Protein 2 Coordinates Early Tooth Mineralization

2018 ◽  
Vol 97 (7) ◽  
pp. 835-843 ◽  
Author(s):  
Z. Malik ◽  
M. Alexiou ◽  
B. Hallgrimsson ◽  
A.N. Economides ◽  
H.U. Luder ◽  
...  
Keyword(s):  
Tooth Development ◽  
Bmp Signaling ◽  
Conditional Knockout ◽  
Bone Morphogenetic Protein 2 ◽  
Micro Computed Tomography ◽  
Tooth Mineralization ◽  
Morphogenetic Protein ◽  
Dental Hard Tissues ◽  
Dentin Sialoprotein ◽  
Tooth Germs

Formation of highly organized dental hard tissues is a complex process involving sequential and ordered deposition of an extracellular scaffold, followed by its mineralization. Odontoblast and ameloblast differentiation involves reciprocal and sequential epithelial-mesenchymal interactions. Similar to early tooth development, various Bmps are expressed during this process, although their functions have not been explored in detail. Here, we investigated the role of odontoblast-derived Bmp2 for tooth mineralization using Bmp2 conditional knockout mice. In developing molars, Bmp2LacZ reporter mice revealed restricted expression of Bmp2 in early polarized and functional odontoblasts while it was not expressed in mature odontoblasts. Loss of Bmp2 in neural crest cells, which includes all dental mesenchyme, caused a delay in dentin and enamel deposition. Immunohistochemistry for nestin and dentin sialoprotein (Dsp) revealed polarization defects in odontoblasts, indicative of a role for Bmp2 in odontoblast organization. Surprisingly, pSmad1/5/8, an indicator of Bmp signaling, was predominantly reduced in ameloblasts, with reduced expression of amelogenin ( Amlx), ameloblastin ( Ambn), and matrix metalloproteinase ( Mmp20). Quantitative real-time polymerase chain reaction (RT-qPCR) analysis and immunohistochemistry showed that loss of Bmp2 resulted in increased expression of the Wnt antagonists dickkopf 1 ( Dkk1) in the epithelium and sclerostin ( Sost) in mesenchyme and epithelium. Odontoblasts showed reduced Wnt signaling, which is important for odontoblast differentiation, and a strong reduction in dentin sialophosphoprotein ( Dspp) but not collagen 1 a1 ( Col1a1) expression. Mature Bmp2-deficient teeth, which were obtained by transplanting tooth germs from Bmp2-deficient embryos under a kidney capsule, showed a dentinogenesis imperfecta type II–like appearance. Micro–computed tomography and scanning electron microscopy revealed reduced dentin and enamel thickness, indistinguishable primary and secondary dentin, and deposition of ectopic osteodentin. This establishes that Bmp2 provides an early temporal, nonredundant signal for directed and organized tooth mineralization.

scholarly journals The concurrent stimulation of Wnt and FGF8 signaling induce differentiation of dental mesenchymal cells into odontoblast-like cells

2021 ◽  
Author(s):  
Motoyoshi Kimura ◽  
Akiko Saito ◽  
Shoko Onodera ◽  
Takashi Nakamura ◽  
Makoto Suematsu ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Tooth Development ◽  
Tooth Germ ◽  
Mesenchymal Cells ◽  
Dentin Matrix Protein ◽  
Fibroblast Growth Factor 8 ◽  
Related Transcription Factor ◽  
Tooth Germs ◽  
Canonical Wnt ◽  
Stimulation Of

AbstractFibroblast growth factor 8 (FGF8) is known to be a potent stimulator of canonical Wnt/β-catenin activity, an essential factor for tooth development. In this study, we analyzed the effects of co-administration of FGF8 and a CHIR99021 (GSK3β inhibitor) on differentiation of dental mesenchymal cells into odontoblasts. Utilizing Cre-mediated EGFP reporter mice, dentin matrix protein 1 (Dmp1) expression was examined in mouse neonatal molar tooth germs. At birth, expression of Dmp1-EGFP was not found in mesenchymal cells but rather epithelial cells, after which Dmp1-positive cells gradually emerged in the mesenchymal area along with disappearance in the epithelial area. Primary cultured mesenchymal cells from neonatal tooth germ specimens showed loss of Dmp1-EGFP positive signals, whereas addition of Wnt3a or the CHIR99021 significantly regained Dmp1 positivity within approximately 2 weeks. Other odontoblast markers such as dentin sialophosphoprotein (Dspp) could not be clearly detected. Concurrent stimulation of primary cultured mesenchymal cells with the CHIR99021 and FGF8 resulted in significant upregulation of odonto/osteoblast proteins. Furthermore, increased expression levels of runt-related transcription factor 2 (Runx2), osterix, and osteocalcin were also observed. The present findings indicate that coordinated action of canonical Wnt/β-catenin and FGF8 signals is essential for odontoblast differentiation of tooth germs in mice.

Hybrid odontogenic tumor of calcifying odontogenic cyst and ameloblastic fibroma

2004 ◽  
Vol 98 (1) ◽  
pp. 80-84 ◽  
Author(s):  
Jung Hoon Yoon ◽  
Hyung Jun Kim ◽  
Jong In Yook ◽  
In Ho Cha ◽  
Gary L Ellis ◽  
...  
Keyword(s):  
Odontogenic Cyst ◽  
Odontogenic Tumor ◽  
Calcifying Odontogenic Cyst ◽  
Ameloblastic Fibroma

Opg, Rank, and Rankl in Tooth Development: Co-ordination of Odontogenesis and Osteogenesis

2004 ◽  
Vol 83 (3) ◽  
pp. 241-244 ◽  
Author(s):  
A. Ohazama ◽  
J.-M. Courtney ◽  
P.T. Sharpe
Keyword(s):  
Tooth Development ◽  
Nuclear Factor Κb ◽  
Cellular Interactions ◽  
Rankl Expression ◽  
Dental Papilla ◽  
Spatiotemporal Expression ◽  
Receptor Activator ◽  
Explant Cultures ◽  
Enamel Epithelium ◽  
Tooth Germs

Osteoprotegerin (OPG), receptor activator of nuclear factor-κB (RANK), and RANK ligand (RANKL) are mediators of various cellular interactions, including bone metabolism. We analyzed expression of these three genes during murine odontogenesis from epithelial thickening to cytodifferentiation stages. Opg showed expression in the thickening and bud epithelium. Expression of Opg and Rank was observed in both the internal and the external enamel epithelium as well as in the dental papilla mesenchyme. Although Rankl expression was not detected in tooth epithelium or mesenchyme, it was expressed in pre-osteogenic mesenchymal cells close to developing tooth germs. All three genes were detected in developing dentary bone at P0. The addition of exogenous OPG to explant cultures of tooth primordia produced a delay in tooth development that resulted in reduced mineralization. We propose that the spatiotemporal expression of these molecules in early tooth and bone primordia cells has a role in co-ordinating bone and tooth development.

scholarly journals The effect of unilateral and bilateral laparoscopic surgery for endometriosis on Anti-Mullerian Hormone (AMH) level after 3 and 6 months: a systematic review and meta-analysis

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Anisodowleh Nankali ◽  
Mohsen Kazeminia ◽  
Parnian Kord Jamshidi ◽  
Shamarina Shohaimi ◽  
Nader Salari ◽  
...  
Keyword(s):  
Systematic Review ◽  
Laparoscopic Surgery ◽  
Growth Factors ◽  
Web Of Science ◽  
Meta Analysis ◽  
Research Work ◽  
Mean Difference ◽  
Transient Growth ◽  
Common Causes ◽  
Standardized Mean Difference

Abstract Background Endometriosis is one of the most common causes of infertility. The causes of the disease and its definitive treatments are still unclear. Moreover, Anti-Mullerian Hormone (AMH) is a glycoprotein dimer that is a member of the transient growth factors family. This research work aimed to identify the effect of unilateral and bilateral laparoscopic surgery for endometriosis on AMH levels after 3 months, and 6 months, using meta-analysis. Methods In this study, the articles published in national and international databases of SID, MagIran, IranMedex, IranDoc, Cochrane, Embase, Science Direct, Scopus, PubMed, and Web of Science (ISI) were searched to find electronically published studies between 2010 and 2019. The heterogeneous index between studies was determined using the I2 index. Results In this meta-analysis and systematic review, 19 articles were eligible for inclusion in the study. The standardized mean difference was obtained in examining of unilateral laparoscopic surgery for endometriosis (before intervention 2.8 ± 0.11, and after 3 months 2.05 ± 0.13; and before intervention 3.1 ± 0.46 and after 6 months 2.08 ± 0.31), and in examining bilateral laparoscopic surgery for endometriosis examination (before intervention 2.0 ± 08.08, and after 3 months 1.1 ± 0.1; and before intervention 2.9 ± 0.23 and after 6 months 1.4 ± 0.19). Conclusion The results of this study demonstrate that unilateral and bilateral laparoscopic surgery for endometriosis is effective on AMH levels, and the level decreases in both comparisons.

scholarly journals PHYSICAL EXERCISE IN THE PROMOTION OF GENE THERAPY AUXILIARY EFFECT

2021 ◽  
Vol 27 (8) ◽  
pp. 779-782
Author(s):  
Wei Shen ◽  
Xiaojun Liang
Keyword(s):  
Gene Therapy ◽  
Growth Factors ◽  
Growth Factor ◽  
Physical Exercise ◽  
Fracture Healing ◽  
Bone Morphogenetic Protein ◽  
Bone Growth ◽  
Transforming Growth Factor ◽  
Transforming Growth Factors ◽  
Morphogenetic Protein

ABSTRACT Introduction: In recent years, genetic engineering has made outstanding contributions to sports, and it has played a huge role in promoting the development of sports-related fields. Objective: We analyze the tissue source of bone growth and healing by studying the role of bone morphogenetic protein and transforming growth factors in fracture injuries caused by sports. Methods: We established a human fracture model to express the shape and content of bone morphogenetic protein and transforming growth factor during fracture healing. Results: In the fracture healing stage caused by different sports, the expression levels of the two genes are different. Bone morphogenetic protein has a high content in the osteogenesis stage of the membrane, while transforming growth factor is high in the cartilage ossification stage. Conclusion: Gene therapy for fractures caused by physical exercise has certain advantages. Osteoblasts and chondrocytes are involved in the synthesis of transforming growth factors. Level of evidence II; Therapeutic studies - investigation of treatment results.

scholarly journals Calcifying odontogenic cyst associated with an antral pseudocyst: treatment of an uncommon case report and update of main findings

2021 ◽  
Vol 62 (2) ◽  
Author(s):  
Glória França ◽  
◽  
Dáurea Sena ◽  
Juliana Pinheiro ◽  
Rodrigo Rodrigues ◽  
...  
Keyword(s):  
Excisional Biopsy ◽  
Odontogenic Cyst ◽  
Odontogenic Cysts ◽  
Histopathological Diagnosis ◽  
Alveolar Ridge ◽  
Calcifying Odontogenic Cyst ◽  
First Case ◽  
Tumor Lesion ◽  
Uncommon Case

A calcifying odontogenic cyst may be associated with odontogenic tumors, particularly odontomas. However, the association between calcifying odontogenic cysts and odontogenic cysts is rare. This study aims to report the first case of a calcifying odontogenic cyst associated with an antral pseudocyst. A male patient presented a tumor lesion in his right maxillary alveolar ridge with 6 months of evolution and painful symptoms . An excisional biopsy was performed, and a histopathological diagnosis of calcifying odontogenic cyst associated with an antral pseudocyst was issued. The treatment of choice was lesion enucleation and curettage. The patient has been under follow-up for about 3 years without lesion recurrence, which is typical indolent calcifying odontogenic cyst behavior.

scholarly journals Differential Expression of Claudin in Odontogenic Cysts

2021 ◽  
Author(s):  
Ekarat Phattarataratip ◽  
Kraisorn Sappayatosok
Keyword(s):  
Pairwise Comparison ◽  
Odontogenic Cyst ◽  
Odontogenic Cysts ◽  
Positive Staining ◽  
Pathogenic Role ◽  
Dentigerous Cysts ◽  
Different Types ◽  
Level Of Significance ◽  
Post Hoc ◽  
Spearman’S Correlation

Abstract Objective This study aimed to analyze claudin-1, -4, and -7 expression in different types of odontogenic cysts (odontogenic keratocysts [OKCs], dentigerous cysts [DCs], calcifying odontogenic cysts [COCs], and radicular cysts [RCs]) as well as its association with OKC recurrence. Materials and Methods Seventy samples of odontogenic cysts samples were immunohistochemically stained to detect claudin-1, -4, and -7 expression. Patient information and OKC recurrence data were recorded. The staining was analyzed semiquantitatively and categorized based on the pattern and percentage of positively stained cystic epithelial cells. Statistical Analysis Expression of different claudins between groups was analyzed using the Kruskal–Wallis test with Dunn's test, followed by post hoc pairwise comparison. The association between claudin expression and OKC recurrence was analyzed by the Mann–Whitney U test. Correlations among claudin expression were examined with Spearman's correlation coefficient. Level of significance was at p < 0.005. Results Claudin-1 was widely expressed in every odontogenic cyst. Most DCs (50%) expressed claudin-1 in more than 75% of cells, as did RCs (65%), while most OKCs (50%) expressed claudin-1 in 26 to 50% of cells. Most COCs (50%) expressed claudin-1 in 51 to 75% of cells. Every sample of OKC and RC was positive for claudin-4, but no sample showed staining in more than 51% of cells. Every odontogenic cyst was positive for claudin-7. DCs (35%), OKCs (55%), and RCs (40%) mostly showed staining in 26 to 50% of cells. High claudin-1 expression was shown in COCs, DCs, and RCs, while low expression of claudin-4 was shown in every odontogenic cyst. For claudin-7, the expression is high only in COCs. Claudin-1 and -4 was significantly different among each odontogenic cyst. High expression of claudin-1 was correlated with OKC recurrence. The correlations of claudin-1 with claudin-7 expression and claudin-4 with claudin-7 expression were significant in DCs. In COCs, claudin-1 and claudin-7 expression was significantly correlated. Conclusions The expression of claudin-1, -4, and -7 was present in every odontogenic cyst, but the proportion of positive staining cells was different. Expression of claudin-1 is associated with OKC recurrence. Dysregulation of claudin expression may play a pathogenic role in cyst pathogenesis.

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